**Aflatoxin B1 - Prevention of Its Genetic Damage by Means of Chemical Agents**

Eduardo Madrigal-Bujaidar1, Osiris Madrigal-Santillán2, Isela Álvarez-González1 and Jose Antonio Morales-González2

*1Laboratorio de Genética, Escuela Nacional de Ciencias Biológicas, IPN, 2Instituto de Ciencias de la Salud, UAEH, México* 

#### **1. Introduction**

250 Aflatoxins – Detection, Measurement and Control

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Mycotoxins are structurally diverse groups largely composed of small molecular weight chemicals, which are generally produced by the mycelial structure of filamentous fungi. These toxins are secondary metabolites mainly synthesized during the end of the mould exponential phase of growth. They appear to have no biological significance with respect to their growth/development or competitiveness, but when ingested by higher vertebrates and other animals they can cause diseases called mycotoxicoses (Kabak et al., 2006; Madrigal-Santillán et al., 2010). Aflatoxin B1 (AFB1), in particular, is a tetrahydrofuran moiety fused to a coumarin ring and was chemically classified as cyclopenta[c]furo[3',2':4,5]furo[2,3h][1] benzopyran-1,11-dione,2,3,6a,9a-tetrahydro-4-methoxy-, (6aR,9aS) (Eaton et al., 1994; Hedayati et al., 2007) (Figure 1).

Fig. 1. Chemical structure of aflatoxin B1

The compound is a pale-white to yellow crystalline, odorless solid, soluble in water and in polar organic solvents, such as methanol, chloroform, acetone, acetonitrile, and dimethyl sulfoxide. It has a molecular weight of 312.3, a melting point between 268-269°C, and shows a blue fluorescence in the presence of ultraviolet light (Eaton et al., 1994; Hussein & Brasel, 2001). This secondary metabolite is produced by several strains of filamentous ascomycetes fungi, mainly *Aspergillus flavus* and *Aspergillus parasiticus* (Table 1) which are ubiquitous in the environment and highly resistant to heat and drying. They are saprophytic and frequently live in soil, vegetation, and feeds, acquiring nutrients from dead plants and animal matter.

Aflatoxin B1 - Prevention of Its Genetic Damage by Means of Chemical Agents 253

There are diverse criteria for assessing the economic impact of aflatoxins. These include loss of human and animal life, health care and veterinary care costs, loss of livestock production, loss of forage crops and feeds, regulatory costs, and research cost focusing on relieving the impact and severity of the aflatoxin problem. However, most reports on the matter are on a

With regard to the heavy impact of AFB1 contamination, India can be an example of the problem in emerging countries. A study in the Bihar region showed that nearly 51% of the 387 samples tested were contaminated with molds, and that from the 139 samples containing AFB1, 133 had levels above 0.02 mg/kg (Ranjan & Sinha, 1991). In other studies, authors found levels as high as 3.7 mg/kg of AFB1 in groundnut meal used for dairy cattle, as well as 0.05 to 0.4 mg/kg in 21 of 28 dairy feed samples from farms in and around Ludhiana and Punjab (Dhand et al., 1998; Phillips et al., 1996). Also, in raw peanut oil 65-70 % of AFB1 was found in the sediment and 30-35 % in the supernatant oil after centrifugation (Banu & Muthumary, 2010a). In this context, groundnut contamination was estimated to represent about a 10 million dollar loss in India's export within a decade (Hussein & Brasel, 2001; Vasanthi & Bhat, 1998). Regarding the extent of the problem in developing countries, Table 2 shows that a wide range of commodities are contaminated, even to a higher degree

In Mexico the main contaminated crop is corn. This is a logical situation considering that the country has one of the highest rates of human consumption of this grain in the world (120 kg per capita per year) with a production of about 10.2 million tons for human consumption and 5 million tons for animal feed and other industries (Plasencia, 2004). One of the most significant episodes of aflatoxin contamination of maize was probably that which occurred in a northern state (Tamaulipas) in 1989, where levels of the toxin above 0.1 mg/kg were reported in practically all the plants harvested (García & Heredia, 2006). This represents a potential high health risk to the population, because corn is a basic food consumed as tortilla, with a consumption of 325 g per day (Anguiano-Ruvalcaba et al., 2005). However, this is not the only food susceptible to AFB1 that may pose a health risk, because a number of other maize-based foods are part of the Mexican diet. In regard to this contamination a few studies have been made. In kernelled corn for human consumption in the city of Monterrey, AFB1 was determined in 36 of the 41 samples tested, with concentrations ranging from 5 to 465 ng/g, with 59% of those samples above the Mexican legal limit of 0.02 mg/kg (Torres-Espinoza et al., 1995). Another study in 66 stored samples of maize and wheat in the state of Sonora showed 13 samples (20%) contaminated with AFB1, although the level was higher than 0.02 mg/kg in only one sample (Ochoa et al., 1989). Some general explanations for the contamination in the country are the following: 1- inadequate pre-harvest and storage management, as well as distribution procedures that may favor the development of *Aspergillus*; 2- corn growing under non-irrigation conditions in many places, predisposing plants to drought stress and mold infection; 3- limited possibilities of modern agricultural practices for low income farmers; 4- legal restriction for the use of transgenic maize manifesting insecticidal proteins or any other trait to reduce aflatoxin contamination; 5-infestation with the microleopterans *Carpophilus freemani*, the sap beetle, *Sitophilus zeamais*, the maize weevil, and *Cathartus quadricollis*, square-necked grain beetle, which may facilitate spore entry in the cobs; 6- growth of pollinated varieties which appear to be more prone to disease development and to the effect of environmental factors in comparison with maize hybrids

single aspect of aflatoxin exposure or contamination.

than usually allowed (Williams et al., 2004).

(Figueroa, 1999; Plasencia, 2004; Zuber et al., 1983).

Their spores are produced in large numbers and are spread widely by air currents. These molds grow within many commodities when temperatures are between 24-35 °C, and the moisture content exceeds 7% -10% (Kogbo et al., 1985; Williams et al., 2004).

The present chapter has the purpose of putting into perspective the worldwide relevance of the AFB1 contamination problem due to its effect on the aspects of economy and health, as well as to review the main strategies developed for coping with such contamination. In particular, we discuss the theoretical grounds and the practical approaches which have been carried out by using antimutagenesis and chemoprevention strategies. In these areas are included a description and discussion of the more relevant agents tested against the genotoxic and carcinogenic damage induced by AFB1.
